Jiadifenolide
# Jiadifenolide

Jiadifenolide is a sesquiterpenoid natural product with neurotrophic activity, found in Illicium jiadifengpi. Its biological activity and congested polycyclic structure have made it a popular target for total synthesis.

## Isolation and bioactivity

The seco-prezizaane-type sesquiterpenoid jiadifenolide was isolated in 2009 from the fruit of the flowering plant Illicium jiadifengpi. Chemical synthesis enabled preliminary assessment of its in vitro activity in promoting neurite outgrowth.

## Chemical synthesis

Jiadifenolide has been the subject of synthetic study in several academic labs.

The first total synthesis, reported in 2009, employed an asymmetric Robinson annulation and a translactonization reaction to construct the core of the molecule. Two further syntheses, a chiral-pool approach from (+)-pulegone and a racemic synthesis relying on a samarium diiodide–mediated reductive cyclization, were reported almost simultaneously in 2014. A second chiral-pool synthesis (from (+)-citronellal) reported in 2015 shortened the synthetic sequence, with a double Michael addition as the key transformation of eight steps, allowing the synthesis of gram-scale quantities of jiadifenolide.

